Protein discovered by UT engineers holds promise for antibiotic research

A group of researchers at The University of Texas at Austin and Stanford University has isolated a protein whose effect on RNA in cells could lead to the isolation of new antibiotics.

Dr. George Georgiou, professor of chemical engineering and biomedical engineering, and his collaborators report on the new protein, called RraA, in the Sept. 5 issue of the journal Cell. Their paper represents five years of work by researchers at The University of Texas at Austin and Stanford.

The newly isolated protein kills bacteria by allowing an excessive buildup of RNA and proteins to occur in bacterial cells. By interfering with a bacterial cell’s natural process of RNA buildup and breakdown, the protein causes a lethal amount of RNA proliferation to occur, thus creating a sort of cellular suicide.

“The research is very significant in terms of our knowledge of how proteins are made in cells and how they respond to the environment,” says Georgiou. “It wasn’t known until now that cells use proteins to globally modulate RNA degradation. The protein we discovered affects the level of over 2,000 RNAs in different species, about 50 percent of the total number of different RNAs synthesized in E.coli bacteria.”

In protein synthesis within cells, a piece of genetic information is taken from DNA, the cell’s genetic code, and transcribed into a short-lived molecule called RNA. RNA, in turn, serves as a template for protein synthesis. The RNA specifies which protein will be made and at what level. The amount of protein synthesized at any given moment is controlled by the amount of cellular RNA existing at that moment, a quantity dictated by a balance between RNA synthesis and degradation. In bacteria, RNA degradation is carried out by an enzyme called RNAse E. Georgiou and his coworkers discovered that another protein present in the cell could inhibit RNAse E’s function of routine RNA degradation by binding to it. The researchers named the newly discovered protein RraA. When RraA is produced at a high level, RNA degradation is shut off, proteins are made at abnormal levels and the cells die.

Based on these results, the researchers speculate that the inhibition of RNA degradation represents a bacterium’s “Achilles heel”: Antibiotics that mimic the function of RraA would likely be able to kill bacteria. However, because the mechanism of RNA degradation is fundamentally different in humans they would be unlikely to have adverse effects.

“Having defined a potential target for bacterial killing, we plan to carry out studies to develop small molecules that function in the same way as RraA,” says Georgiou. The next step will be to design smaller, more convenient synthetic proteins with RraA-like qualities, says Georgiou.